A Study to Learn About the Drug-drug Interactions of Sisunatovir in Healthy Adult Participants
- Conditions
- Respiratory Syncytial Virus Infections
- Interventions
- Registration Number
- NCT03782662
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this clinical trial is to learn about the interaction of sisunatovir with four medications (midazolam, itraconazole, rifampicin, and verapamil). These medications are known to have specific effects on enzymes and proteins that could influence drug absorption.
This study will be conducted in 4 Cohorts:
* Cohort 1 will receive midazolam and sisunatovir or placebo,
* Cohort 2 will receive Itraconazole and sisunatovir,
* Cohort 3 will receive verapamil and sisunatovir,
* Cohort 4 will receive rifampicin and sisunatovir. A placebo looks like sisunatovir but does not contain any active medicine in it.
This study is looking for health adult participants that meet the following criteria:
1. Caucasians age 18 to 45 years
2. All fertile participants must agree to the use of highly effective contraception
3. Body mass index (BMI) of 18-25.0 kg/m2
4. Male and female participants who are overtly healthy as determined by medical evaluation. This includes medical history, physical examination, blood pressure, pulse rate, standard 12-lead ECG (electrocardiogram), and laboratory tests.
This study consists of 2 parts, Part A and Part B. Part A will enroll up to 104 participants. The design of Part B will be determined after the completion of Part A.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- Age 18 to 45 years, inclusive
- Willing to comply with protocol defined contraception requirements
- In good health with no history of major medical conditions
- A body mass index (BMI) of 18 - 25 kg/m2
- Evidence of any clinically significant or currently active major medical condition
- Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab)
- Not willing to comply with protocol defined restrictions for intake of drugs of abuse, alcohol, nicotine-containing products, medication (prescription, OTC, herbal, vitamins/minerals etc) and specified food and drink products
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description RV521 plus Rifampicin RV521 RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive Placebo plus Midazolam Placebo for RV521 Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15 RV521 plus Itraconazole RV521 RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive RV521 plus Verapamil RV521 RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive RV521 plus Midazolam RV521 RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15 RV521 plus Itraconazole Itraconazole RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D7 plus Itraconazole 100 mg capsules for oral administration, a 200 mg dose administered once daily on D4 - D10, inclusive RV521 plus Verapamil Verapamil RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D11 plus Verapamil, 80 mg tablets for oral administration, an 80 mg dose administered TDS daily on D4 - D14, inclusive RV521 plus Rifampicin Rifampicin RV521 drug substance in capsule for oral administration, a single 200 mg dose administered on D1 and a single 200 mg dose administered on D10 plus Rifadin, Rifampicin, 300 mg capsules for oral administration, a 600 mg dose administered once daily on D4 - D10, inclusive RV521 plus Midazolam Midazolam RV521 drug substance in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15 Placebo plus Midazolam Midazolam Placebo for RV521 in capsule for oral administration, 200 mg dose administered BID on D2 - D15, inclusive plus Buccolam 10 mg oromucosal solution of midazolam, oral syringes, a single 10 mg dose administered on D1 and a single 200 mg dose administered on D15
- Primary Outcome Measures
Name Time Method Effect of RV521 on Cmax of Midazolam Baseline to study day 17 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on CL/F of Midazolam Baseline to study day 17 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on tmax of Midazolam Baseline to study day 17 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on t1/2 of Midazolam Baseline to study day 17 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on Cmax of RV521 Baseline to study day 16 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of RV521 on AUC of Midazolam Baseline to study day 17 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on Cmax of RV521 Baseline to study day 12 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on tmax of RV521 Baseline to study day 12 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on t1/2 of RV521 Baseline to study day 12 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on CL/F of RV521 Baseline to study day 12 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on tmax of RV521 Baseline to study day 16 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on t1/2 of RV521 Baseline to study day 16 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on AUC of RV521 Baseline to study day 16 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of verapamil on CL/F of RV521 Baseline to study day 16 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of itraconazole on AUC of RV521 Baseline to study day 12 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on Cmax of RV521 Baseline to study day 15 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on tmax of RV521 Baseline to study day 15 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on t1/2 of RV521 Baseline to study day 15 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on CL/F of RV521 Baseline to study day 15 The specified pharmacokinetic parameter will be summarised using descriptive statistics
Effect of rifampicin on AUC of RV521 Baseline to study day 15 The specified pharmacokinetic parameter will be summarised using descriptive statistics
- Secondary Outcome Measures
Name Time Method Number of subjects with treatment-related adverse events as assessed by NCI CTCAE V5.0 Screening to final study visit (performed at 7 days following the last dose of any intervention) The number of subjects with treatment-related adverse events will be summarised by treatment group using descriptive statistics
Number of subjects with QT/QTc interval changes relative to baseline who received RV521 (monotherapy), Midazolam (monotherapy) or RV521 and Midazolam (combination therapy) Baseline to to final study visit (performed at 7 days following the last dose of any intervention) Descriptive statistics will be given by time point and dose-group for absolute values and change from baseline. Results will be tabulated and for QTc, the difference to time matched placebo will also be displayed
Trial Locations
- Locations (1)
Richmond Pharmacology Ltd
🇬🇧London, United Kingdom